Avibactam, which is one of diazabicyclooctanone compounds, as a non-β-lactam inhibitor, may inhibit type A (including ESBL and KPC) and type C of β-lactamases. When co-administered with various types of cephalosporins and carbapenem antibiotics, avibactam has a broad-spectrum activity against bacteria, particularly has a significant activity against Escherichia coli and Klebsiella pneumoniae containing extended-spectrum β-lactamases, Escherichia coli containing surplus AmpC enzyme, and Escherichia coli containing both AmpC and extended-spectrum β-lactamases. Avibactam (I), [(1R,2S,5R)-2-(aminocarbonyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl] sodium sulphate with CAS No. 1192491-61-4, has a structural formula represented by Formula I:

Patent literatures CN103649051A, CN105294690A, CN106866668A, WO2012086241, U.S. Pat. Nos. 8,148,540, 9,284,273, and 9,567,335 disclosed preparation of (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo [3.2.1] octane-2-formamide by use of 5R-[(benzyloxy) amino] piperidine-2S-carboxylate oxalate (III) as the raw material via a route of amidation followed by urea cyclization or a route of urea cyclization followed by amidation, and then the prepared (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo [3.2.1] octane-2-formamide was subjected to debenzylation by palladium-on-carbon catalytic hydrogenolysis, followed by sulphation by sulfur trioxide complex, ammonium salinization, and ion exchange, thereby producing avibactam (I), referring to Scheme 1.

1. In the process of amidation followed by urea cyclization, firstly 5R-[(benzyloxy) amino] piperidine-2S-carboxylate oxalate (III) is amidated by an ammonia-methanol solution or an ammonium hydroxide-alcohol solution to obtain (2S,5R)-5-[(benzyloxy)amino]piperidine-2-formamide; then (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-formamide (with a total yield of 61.2%˜89.1%) is obtained through steps of protection of the amino of piperidine ring by 9-fluorenylmethyl chloroformate (FMOC-CL) or di-tert-butyl dicarbonate, reacting carbonyl diimidazole with benzyloxylamine via carbonylation, deprotection of the piperidine ring by diethylamine, and then urea cyclization.
In this process, amide group is present after amidation, such that it is demanding on urea cyclization reaction, where inexpensive and readily accessible triphosgene or diphosgene cannot be used. This is because under the action of triphogene or diphosgene, amide groups are easily dehydrated to produce cyanide; with a high content of byproducts and difficulty to purify, referring to Scheme 2.

Even if carbonyl diimidazole (CDI) with a high selectivity is used as the urea cyclization reagent, the 9-fluorenylmethyl chloroformate (FMOC-CL) or di-tert-butyl dicarbonate is still needed to protect the aminos of piperidine ring; otherwise, because carbonyl diimidazole and the two aminos (amino of piperidine ring and benzyloxylamino) have similar reaction activities, producing derivatives where imidazole carbonyl is introduced on the two nitrogen atoms with the molar ratio of the two derivatives being about 1:1, while the imidazole carbonyl of the piperidine ring preferably reacts with the ortho-position carboxamide group, the target product cannot be obtained, and the product yield is lower than 50%, referring to Scheme 3:

9-fluorenylmethyl chloroformate (FMOC-CL) or di-tert-butyl dicarbonate protecting agent has a high price; besides, they only provide one carbonyl group; therefore, the reaction atomic economy is poor and the operation process is tedious.
2. In the process of urea cyclization followed by amidation, (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxy acid is obtained through steps of urea cyclization of 5R-[(benzyloxy) amino] piperidine-2S-carboxylate oxalate (III) by a urea cyclization reagent (triphosgene-organic base, carbonyl diimidazole or other carbonylation agent) followed by hydrolysis in an alkaline condition such as lithium hydroxide aqueous solution; and then (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-formamide is obtained through steps of activating carboxyl into anhydrides by trimethylacetyl chloride or other reagent, followed by amidation by the ammonium hydroxide, with a total yield of 34.5-65.5%. Benzyl (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo [3.2.1] octane-2-carboxylate obtained after urea cyclization has a low activity, which cannot be amidated in an ammonia-methanol solution; instead, an effective amidation can only be realized by first hydrolysis of the ester group into carboxyl and then activating the carboxyl into anhydrides; therefore, more operation steps are involved.
Therefore, neither of the processes above facilitates simple industrial production of the intermediate for avibactam, namely, ({[(2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl]oxy}sulfonyl)tetrabutylammonium salt (II).